Authors
Eckel, JasonLavin, Peter J
Finch, Elizabeth A
Mukerji, Nirvan
Burch, Jarrett
Gbadegesin, Rasheed
Wu, Guanghong
Bowling, Brandy
Byrd, Alison
Hall, Gentzon
Sparks, Matthew
Zhang, Zhu Shan
Homstad, Alison
Barisoni, Laura
Birbaumer, Lutz
Rosenberg, Paul
Winn, Michelle P
Affiliation
Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.Issue Date
2011-03MeSH
AlbuminuriaAngiotensin II
Animals
Calcium
Disease Models, Animal
Hypertension
Injections, Subcutaneous
Kidney
Male
Mice
Mice, Knockout
Patch-Clamp Techniques
Podocytes
TRPC Cation Channels
Metadata
Show full item recordCitation
TRPC6 enhances angiotensin II-induced albuminuria. 2011, 22 (3):526-35 J. Am. Soc. Nephrol.Journal
Journal of the American Society of Nephrology : JASNDOI
10.1681/ASN.2010050522PubMed ID
21258036Additional Links
http://www.ncbi.nlm.nih.gov/pubmed?term=TRPC6%20enhances%20angiotensin%20II-induced%20albuminuria.%20Abstract
Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cell-membrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.Item Type
ArticleLanguage
enISSN
1533-3450ae974a485f413a2113503eed53cd6c53
10.1681/ASN.2010050522